Glioblastoma
Conditions
Brief summary
This is a prospective, randomized, open-label, multicenter phase II study. Newly-diagnosed primary glioblastoma patients who have undergone maximal safe resection or biopsy and completed standard concurrent chemoradiotherapy will be enrolled. Subjects will be randomized 1:1 into Arm A (Adebrelimab + Temozolomide + Hyperbaric Oxygen Therapy) or Arm B (Adebrelimab + Temozolomide). The primary endpoint is progression-free survival(PFS). Secondary endpoints include overall survival(OS), objective response rate(ORR), disease control rate(DCR), change of KPS score, safety including TRAE, irAE and SAE. Exploratory objectives include correlation analysis between baseline clinical characteristics / hyperbaric-oxygen-related biomarkers and efficacy-safety outcomes.
Interventions
DRUGAdebrelimab
1200 mg intravenous infusion on Day2 of each 28-day cycle, up to 12 months.
DRUGTemozolomide
Oral, Cycle 1:150 mg/m² d2-d6; Cycle 2-12: 200 mg/m² d2-d6, q28d; minimum 6 cycles, maximum12 cycles.
PROCEDUREProcedure:Hyperbaric Oxygen Therapy
2ATA absolute pressure, 90 minutes once daily, Day1-7 per 28-day cycle. Adebrelimab infusion shall be completed within 24 hours after HBOT.
Sponsors
Wei Jiang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-70 years, male or female. * Newly-diagnosed primary glioblastoma histologically-confirmed; received maximal safe resection or biopsy, and completed standard concurrent chemoradiotherapy with temozolomide. * Dexamethasone dose ≤4 mg/day at initiation of adjuvant study treatment. * Karnofsky Performance Status(KPS) ≥70. * Expected survival ≥3 months. * Adequate bone marrow: ANC ≥1.5×10\^9/L; Hb ≥90 g/dL; PLT ≥100×10\^9/L; WBC ≥3.0×10\^9/L. * Adequate liver function: ALT/AST/ALP ≤2.5×ULN (≤5×ULN if liver metastasis); total bilirubin \<1.5×ULN. * Adequate coagulation function: PT, APTT, INR ≤1.5×ULN. * Female not pregnant / lactating; effective contraception required for fertile females and males during study and 6-month after last study treatment. * Signed written informed consent, willing to comply with study procedures. * Not participating in other interventional clinical trials.
Exclusion criteria
* Prior anti-angiogenic, targeted, immunotherapy (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, CTLA-4 antibody etc.). * Progressive disease according to iRANO criteria. Suspicious pseudo-progression should be further evaluated by advanced imaging. * Multifocal glioblastoma (separate tumor lesions without overlapping T2/FLAIR signal), or leptomeningeal metastasis. * Prior interstitial brachytherapy, implanted chemotherapy, local injection, convection-enhanced delivery; prior Gliadel wafer placement; prior Optune device usage. * Tumor completely located in infratentorial region. * Known hypersensitivity to temozolomide or adebrelimab components. * Dexamethasone \>4 mg/day at adjuvant treatment initiation. * History of immunodeficiency, or receiving immunosuppressive agents within 7 days before first study drug (except dexamethasone ≤4 mg daily). * Uncontrolled concurrent severe disease: active infection, symptomatic congestive heart failure, unstable angina, arrhythmia, uncontrolled hypertension or psychiatric condition interfering with study compliance. * Active systemic autoimmune disease requiring systemic therapy within past 2 years; physiological replacement therapy (thyroxine, insulin etc.) are allowed. * Medical conditions unsuitable for hyperbaric oxygen therapy or immunotherapy. * Severe anemia or concomitant medications interfering temozolomide absorption. * Uncontrolled major psychiatric disorder including depression with CESD-R score ≥16. * Cognitive impairment preventing neuro-oncology assessment. * Pregnant or lactating women. * Participated in other relevant clinical trials within prior 3 months. * Life-threatening complication or vegetative state after chemoradiotherapy. * Other malignant tumor within past 5 years (except cured carcinoma in-situ, basal-cell skin carcinoma). Poor compliance unable to follow protocol. * Substance-use disorder (DSM-V criteria: alcohol or drug addiction). * Active cardiac disease within 6 months prior to screening: myocardial infarction, unstable angina; LVEF\<50%, poorly controlled arrhythmia. * Active infection or unexplained fever\>38.5℃ at screening / before first dosing (fever attributed to tumor is permitted). * Immunodeficiency including active hepatitis; HBV-DNA ≥1000 IU/ml; HCV-RNA ≥1000 IU/ml. Chronic HBV carrier with HBV-DNA\<2000 IU/ml must receive concurrent antiviral treatment to be eligible. * Investigator's judgment that subject is inappropriate for this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From first study treatment, tumor imaging performed every 6-9 weeks (±7 days) for the first 24 weeks, then every 12 weeks (±7 days); assessed up to 24-months after first study treatment. | Time from first study treatment to disease progression (per iRANO criteria) or death from any cause, whichever occurs first. Subjects without progression/death will be censored at last valid tumor assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From first study treatment; survival follow-up every 3 months (±28 days); assessed up to 24-months after first study treatment | Time from first study treatment to death of any cause. Surviving subjects are censored at date of last survival follow-up. |
| Objective Response Rate (ORR) | Baseline; tumor imaging every 6-9 weeks (±7 days) for first 24 weeks, then every 12 weeks (±7 days); assessed up to 24-months after first study treatment. | Percentage of participants achieving Complete Response (CR) or Partial Response (PR) assessed by iRANO criteria. CR/PR need confirmation ≥4 weeks later. |
| Disease Control Rate (DCR) | Baseline, Day1 of each 28-day treatment cycle, End-of-Treatment visit, follow-up visits; assessed up to 24-months after first study treatment. | Percentage of participants achieving CR, PR or Stable Disease (SD) assessed by iRANO criteria. |
| hange from Baseline in Karnofsky Performance Status (KPS) score | From date of signed informed consent through 90-days after last study drug administration. | Incidence, grade, causality and resolution of TRAE, irAE, SAE. |
Outcome results
None listed